Compositions having a physiological cooling effect are well known in the art. In particular, menthol, which is an alicyclic alcohol, is well known for its physiological cooling effect on the skin and mucous membranes of the mouth, and has been used extensively as a flavoring agent in foodstuffs and beverages, as well as generally in the flavor and fragrance industry. However, although menthol demonstrates an intense cooling effect, menthol also has several disadvantages, including high volatility, strong smell, bitter taste, can produce a burning sensation in high concentrations, and can interfere with other compositions. Accordingly, other physiological coolants derived from menthol have been synthesized in order to try to overcome the deficiencies of menthol.
For example, U.S. Pat. No. 4,157,384 discloses 3-substituted-p-menthanes in which the compositions therein have a carbon-carbon bond in the third position, as opposed to the carbon-hydroxyl bond in menthol. The compounds disclosed in U.S. Pat. No. 4,157,384 are generally known as WS-type coolants, and are generally derived from key synthetic intermediate p-menthane-3-carboxylic acid, which is an alicyclic carboxylic acid compound also known as WS-1.
Synthesis of p-menthane-3-carboxylic acid is also well known in the art, and a process for producing p-menthane-3-carboxylic acid is disclosed in GB 1,392,907. In particular, GB 1,392,907 discloses a process for producing p-menthane-3-carboxylic acid by conventional Grignard reaction techniques, including reacting p-menth-3-yl chloride and magnesium to produce the corresponding Grignard reagent, and then after the Grignard reagent is fully produced, reacting the Grignard reagent with carbon dioxide to produce the corresponding carboxylate magnesium salt (i.e., Grignard reagent/carbon dioxide complex). The carboxylate magnesium salt is then hydrolyzed in acid to produce the resulting alicyclic carboxylic acid compound, p-menthane-3-carboxylic acid.
Although the process of GB 1,392,907 can result in producing p-menthane-3-carboxylic acid (i.e., WS-1), which can then be used as an intermediate to produce other WS-type coolants, the process of GB 1,392,907 has several disadvantages. In particular, the process of GB 1,392,907 is carried out by conventional Grignard reaction techniques in which the menthyl halide is first reacted with magnesium to produce the Grignard reagent, and then, only after all of the menthyl halide is added and reacted to produce the Grignard reagent, the Grignard reagent is then reacted with carbon dioxide to produce the carboxylate magnesium salt. Thereafter, the carboxylate magnesium salt is then hydrolyzed to liberate the carboxylic acid product. Therefore, one of the major disadvantages of the process of GB 1,392,907 is that the process is carried out in multiple separate steps, including first fully producing the Grignard reagent from the reaction between the menthyl halide and magnesium. Then, only after all of the menthyl halide has been added and reacted with the magnesium to produce all of the resultant Grignard reagent, is the Grignard reagent then reacted with carbon dioxide to produce the carboxylate magnesium salt, which is then hydrolyzed to produce the resultant carboxylic acid product. This demarcation of steps between producing all of the Grignard reagent first, and then only after all of the Grignard reagent is produced, reacting the Grignard reagent with carbon dioxide to produce the resultant carboxylate magnesium salt, not only increases the time required to ultimately produce the resultant alicyclic carboxylic acid product, but also increases the amount and complexity of apparatuses required to run the reaction to completion. In fact, many times multiple reaction vessels are required to first produce the Grignard reagent, and then to separately react the Grignard reagent with carbon dioxide to produce the carboxylate magnesium salt.
Accordingly, there remains a need in the art for a process for preparing alicyclic carboxylic acid compounds, whereby the demarcation of steps between first, fully producing the alicyclic Grignard reagent, and then, only after the alicyclic Grignard reagent is fully produced, reacting the alicyclic Grignard reagent with carbon dioxide to produce the corresponding alicyclic carboxylate magnesium salt, is reduced. In particular, there remains a need in the art for a process for preparing alicyclic carboxylic acid compounds, whereby carbon dioxide is concurrently added to a Grignard reaction mixture comprising an alicyclic halide compound, magnesium, and an alicyclic Grignard reagent, while the alicyclic Grignard reagent is still being produced, to produce an alicyclic carboxylate magnesium salt, with the alicyclic Grignard reagent and the alicyclic carboxylate magnesium salt being prepared in a one-pot synthesis (i.e., in a single reaction vessel).